<i>N</i> -Acetylcysteine-Functionalized Gold Nanoparticles via Photoclick Reaction as Antioxidant Nanomedicine

Reactive oxygen species (ROS) are highly reactive molecules regulated by a balance of enzymatic and nonenzymatic antioxidant systems. In the heart, ROS play crucial roles in maintaining cellular homeostasis, influencing processes such as cell proliferation, differentiation, and excitation–contraction coupling. However, when ROS levels surpass the antioxidant defense capacity, oxidative stress occurs, leading to cellular and molecular damage that can ultimately result in cardiac dysfunction. In this study, we developed an antioxidant nanomedicine based on gold nanoparticles (Au NPs) functionalized with N-acetylcysteine (NAC), designed to counteract oxidative stress in the heart. NAC is an essential endogenous antioxidant that can effectively prevent local ROS formation and protect human endothelial and stem cells from oxidative stress. Using a thiol–yne photoclick chemistry approach, NAC was efficiently grafted onto Au NPs prefunctionalized with 4-ethynylbenzene diazonium salts. The resulting Au NPs exhibit excellent biocompatibility, along with significant antioxidant activity, good compatibility with human endothelial cells, and efficient cellular internalization.